In a normal state of health, the human or animal body system continuously maintains physiological balance. Even during times of external influence due to disease, drugs, surgical intervention, trauma, cardiopulmonary bypass and the like, the body system auto regulates in order to maintain physiological balance. To achieve this balance, receptors throughout the body work to monitor and adjust haemodynamic variables such as pressure and flow.
In a non-optimal state of haemodynamic performance and where autoregulation has become impaired, the subject will often enter a state of shock manifesting in low blood pressure. In the clinical setting, the subject is monitored and therapy administered to ensure that there is sufficient flow in the body to reach all vital organs including the brain, heart and kidneys, so as to maintain adequate oxygen delivery to meet the metabolic needs of those organs. Failure to administer appropriate therapy leads to worsening of the patient's condition, ultimately leading to heart failure.
Traditionally, monitoring involves obtaining blood pressure measurements, together with measurements of oxygen saturation, heart rate ECG, and in the most severe cases, measuring cardiac output. Each of these parameters together with the clinician's assessment of physical signs give an indication of the subject's circulatory function e.g. during critical care, anaesthesia and surgery. Changes in circulatory function indicate that therapy must be adjusted in order to restore the function to more optimal values. Given the complexity and interaction of the organs of circulatory system, it is difficult for physicians to determine appropriate treatment when the subject's haemodynamic performance is being monitored using a variety of distinct variables viewed subjectively and individually. The principal obstacle to improving outcomes arises from the lack of a consensus about the appropriate haemodynamic goals in patient management. There is broad agreement that all patients require the same haemodynamic goals, but there is disagreement about which goals (in blood pressure, cardiac output, oxygenation) are critically important.
Physiology text books replicate two curves to describe the physiology of shock as illustrated in FIG. 1. During normal circulation, constant flow is maintained across a range of blood pressures. This is known as the “autoregulatory range”. Although the physiological mechanism for autoregulation is not fully understood, it is believed to be an intrinsic property of muscle (the “myogenic” hypothesis), and/or the result of physiological molecules (the “metabolic” hypothesis) which accumulate as pressure increases, and/or an effect of fluid crossing the barrier of the vessels and exerting increased pressure from outside to maintain flow at the lower level (the “tissue pressure” hypothesis).
Curve I represents the autoregulation curve in the “normal patient” having a mean arterial pressure of between 60 and 130 mmHg (normo-tensive patient). Curve II represents the autoregulation curve in the hypertensive patient. Here, constant flow is maintained at higher pressures hence the blood pressure range across which “autoregulation” occurs is shifted to the right. In the hypertensive patient, instead of auto regulating flow between a pressure range of 60 to 130 mmHg, in the hypertensive patient this range may be 80 to 150 mmHg.
Below the lower end of the autoregulatory range (region A), blood pressure and cardiac output fall. This is accepted to characterise low output hypotension. However, these curves do not describe the subject having high output hypotension (as occurs in sepsis). Instead, physicians have relied on graphical representations originating from the Guyton model. The Guyton model devised in the 1970s relied on the study of small numbers of laboratory animals and now inferior measurement techniques to explain how blood pressure and cardiac output were controlled, in order to devise treatments.
According to Guyton, in the circulation there is a constant matching of venous return (preload) and ventricular function (cardiac output). This is represented in FIG. 2. In the closed system of Guyton, venous return to the heart (Central Venous Pressure (CVP)/Right Arterial Pressure (RAP)) must match volume ejected by the heart. Any central venous pressure value can represent multiple “equilibrium points” between venous return and ventricular function. If venous return is increased the venous return curve shifts right, the central venous pressure is increased and the patient moves “up” the ventricular function curve (VFC). If the patient bleeds, venous return decreases, the curve shifts left and the new equilibrium point occurs at a lower point on the ventricular function curve.
In the clinical setting, physicians rely on individual vital sign monitoring systems as may be applied to the Guyton paradigm in order to determine appropriate therapies for subjects exhibiting characteristics of non-optimal haemodynamic function. Although the Guyton model intuitively matches clinical observations in a steady state situation, it does not adequately explain shock states and fails to account for physiological differences in e.g. the fit versus obese individual and the young versus elderly adult. Further, its use has prompted unproven theories that have been applied in the clinical setting, perhaps to the detriment of patients being treated. These deficiencies have been known for some time. One group of researchers is investigating use of an alternative resuscitation algorithm devised by Rivers (NEJM, 2001) which is the latest manifestation of ‘goal directed therapy’ the goal being to increase oxygen delivery on the as yet unproven assumption that this is the physiological purpose to which vasodilation and increased cardiac output is directed.
It would be desirable to provide an improved approach to monitoring subjects experiencing or likely to experience non-optimal haemodynamic performance. It would also be desirable to improve the manner in which therapies for restoring optimal haemodynamic performance are determined.